Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An anterior operative procedure using a strut of fibular graft material was performed either alone or in combination with a posterior stabilization in five patients with cervical spine instability secondary to neoplastic disease. Osseous tumor was present in four of the five patients (osteoblastoma, metastatic adrenal carcinoma, metastatic renal cell carcinoma, multiple myeloma) and the fifth had spine instability as a result of a posterior decompression for cervical spinal cord glioma. The anterior approach using fibula to replace diseased vertebrae and provide axial support for the neck was a valuable therapeutic modality in this group of patients, all of whom had a limited life expectancy. Cervical spine stability obtained by operative intervention led to a reduction of neck pain and maintenance of ambulation until the neoplastic condition became terminal.
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PMID:Anterior fibular strut graft in neoplastic disease of the cervical spine. 50 8

At our institution, 3 patients with pulsatile sternal tumor have been seen. Although ascending aortic aneurysm frequently is high on the list of differential diagnoses, the likelihood that this tumor is metastatic from either a primary renal or thyroid neoplasm is overwhelming. Of the 15 patients reported, 11 had metastases from a primary renal cell carcinoma, including all 3 of our patients. There were 2 patients with primary myeloma, the only histologically proved primary pulsatile sternal tumor. From the surgical standpoint, only the patient with metastatic renal cell carcinoma has a chance of cure. With the recent report of 2 5-year survivors and our own experience of 1 patient with a long asymptomatic interval following resection of the primary kidney tumor and the secondary sternal metastasis, the attitude of hopelessness for these patients should be challenged and an aggressive approach considered.
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PMID:Pulsatile sternal tumor: report of three cases and a review of the literature. 721 19

The human anti-mouse immunoglobulin antibody (HAMA) response, which occurs frequently after injection of murine monoclonal antibodies (MAb) directed against cellular targets, has been reported extensively in several studies. We analysed here HAMA in 12 patients (six with multiple myeloma, MM, and six with metastatic renal cell carcinoma, MRCC) who were treated with B-E8, an IgG1 MAb against interleukin-6 (IL-6). Efficiency of the treatment was evidenced by the drop in the serum levels of C reactive protein (CRP), of which the in vivo production is under the control of IL-6. Three patients with MM and the six patients with MRCC became immunized to the injected MAb. HAMA appeared between days 7 and 15 after the beginning of the treatment. The nine patients made IgG antibodies; four also made IgM. All of immunized patients made anti-idiotype antibodies specific to B-E8. Two of them also developed HAMA directed to murine IgG1 isotype; in these two patients B-E8 MAb cleared rapidly from the circulation with loss of treatment efficiency. In the patients who developed only anti-idiotype antibodies, serum levels of B-E8 remained unchanged and CRP production remained inhibited, indicating that treatment efficiency was not affected by the presence of HAMA. Circulating B-E8 MAb were still able to bind to IL-6 and to inhibit IL-6-independent proliferation despite the presence of anti-idiotypic HAMA. Therefore, in contrast to HAMA against MAb directed against cellular targets, HAMA against anti-IL-6 MAb idiotopes led neither to clearance nor to functional inactivation of the injected MAb.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunomodulating IL-6 activity by murine monoclonal antibodies. 778 52

We analysed human anti-mouse antibodies (HAMA) in 12 patients (six with multiple myeloma (MM) and six with metastatic renal cell carcinoma (MRCC) who were treated with B-E8, an IgG1 MoAb against IL-6. Efficiency of the treatment was evidenced by the drop in the serum levels of C-reactive protein (CRP), the in vivo production of which is under the control of IL-6. Three patients with MM and the six patients with MRCC became immunized to the injected MoAb. HAMA appeared between days 7 and 15 after the beginning of the treatment. The nine patients made IgG antibodies; four also made IgM. All immunized patients made anti-idiotype antibodies specific to B-E8. Two of them also developed HAMA directed to murine IgG1 isotype; in these two patients B-E8 MoAb cleared rapidly from the circulation with loss of treatment efficiency. In the patients who developed only anti-idiotype antibodies, serum levels of B-E8 remained unchanged and CRP production remained inhibited, indicating that treatment remained efficient in the presence of HAMA. Circulating B-E8 MoAbs were still able to bind to IL-6 and to inhibit IL-6-dependent proliferation despite the presence of anti-idiotypic HAMA. Therefore, in contrast to HAMA produced against MoAb directed against cellular targets, HAMA against anti-IL-6 MoAb idiotopes led neither to clearance nor to functional inactivation of the injected MoAb. This was further shown by resuming the B-E8 treatment with success in a patient who still had anti-idiotypic HAMA.
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PMID:Human anti-mouse antibody response to the injection of murine monoclonal antibodies against IL-6. 795 40

Recent studies have indicated that bone marrow angiogenesis is increased in multiple myeloma, suggesting that treatment with an antiangiogenic agent might be useful. Among the new antiangiogenic drugs in development, Neovastat (AE-941; Aeterna Laboratories, Quebec City, Canada) can be classified as a naturally occurring multifunctional antiangiogenic agent. It has a marked inhibitory effect on the formation of blood vessels in the chicken embryo vascularization assay (EVT) and endothelial cell proliferation. Furthermore, in vivo experiments showed that oral administration of Neovastat blocks the formation of blood vessels in Matrigel implants containing basic fibroblast growth factor (bFGF). The antiangiogenic activity of Neovastat was found to be associated with two mechanisms of action. In addition to the inhibition of the matrix metalloproteinase activities (MMP-2, MMP-9, and MMP-12), Neovastat inhibits vascular endothelial growth factor (VEGF) binding to endothelial cells, VEGF-dependent tyrosine phosphorylation, and VEGF-induced vascular permeability in mice. Neovastat was also found to have a significant antitumor activity. Oral administration of Neovastat in mice with subcutaneous grafted breast cancer (DA3) cells showed a significant reduction in tumor volume. Neovastat also decreased the number of lung metastases in the Lewis lung carcinoma model. Interestingly, the effect of Neovastat was additive to cisplatin in this model. Furthermore, no treatment-related mortality or loss of body weight was observed. Also, toxicology studies in rats and monkeys demonstrate no dose-limiting toxicity or target organ damage after 1 year of chronic exposure, thus suggesting that Neovastat could be safely administered in humans. Four clinical studies have been conducted to establish the dosing, safety, and early efficacy of Neovastat administered orally. In the oncology field, 482 patients have received Neovastat, of which 146 with solid tumors were exposed to the drug for more than 6 months. Two phase III clinical trials are currently underway. A phase III double-blind placebo-controlled study is being conducted to evaluate the efficacy of Neovastat in addition to induction chemotherapy/radiotherapy combined modality treatment in patients with unresectable non-small cell lung cancer stage IIIA and IIIB. A second phase III randomized, double-blind placebo-controlled study evaluates the efficacy of Neovastat as a monotherapy in metastatic renal cell carcinoma patients who have progressed following a first-line immunotherapy. Neovastat efficacy is also being evaluated in a registration phase II trial in patients with early relapse or refractory multiple myeloma.
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PMID:Neovastat, a naturally occurring multifunctional antiangiogenic drug, in phase III clinical trials. 1174 Aug 20

We analyzed toxicity and efficacy of second allogeneic hematopoietic stem cell transplantation (HSCT) or donor lymphocyte infusions (DLI) in 66 patients relapsing with acute myeloid leukemia (n = 15), acute lymphoblastic leukemia (n = 5), chronic myeloid leukemia (n = 14), non-Hodgkin's lymphoma (n = 14), myeloma (n = 8), myelodysplastic syndrome (n = 8), and metastatic renal cell carcinoma (n = 2). Forty-one patients were given second HSCT and 25 DLI. Sixteen patients (39%) are alive and disease-free after a second HSCT including 13 who had received nonmyeloablative conditioning. Thirteen patients (52%) are alive after DLI with mainly chronic myeloid leukemia patients in continuous complete remission. Relapse after HSCT is still a challenging situation and further studies to improve outcome of these patients are warranted.
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PMID:DLI or second transplant. 1261 Oct 68

Six patients underwent segmental bone resection and limb salvage surgery for primary or metastatic bone tumors involving the diaphysis of the femur, the tibia, and the humerus using a modular intramedullary diaphyseal segmental defect fixation system. There were four men and two women with a mean age of 62 years (range: 40-77 years). Histological diagnosis included adamantinoma, synovial sarcoma, multiple myeloma, metastatic renal cell carcinoma, myeloid carcinoma of the thyroid gland, and adenocarcinoma of the stomach. The mean follow-up was 17 months (range: 11-28 months). At the latest examination, five patients were free of local or distant disease and one patient had deceased with distant disease, without evidence of local recurrence. Revision surgery was necessary in one patient because of mechanical loosening of the proximal fixation of the prosthesis at 24 months. The mean postoperative increase of the Enneking rating score was 87.8%. The intramedullary diaphyseal segmental defect fixation system used herein is associated with a satisfactory functional and oncological outcome after wide resection of diaphyseal bone tumors.
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PMID:Limb salvage surgery using the intramedullary diaphyseal segmental defect fixation system. 1934 12